Using Kyte-Doowittwe anawysis,[22] de amino acid seqwence of CD36 predicts a hydrophobic region near each end of de protein warge enough to span cewwuwar membranes. Based on dis notion and de observation dat CD36 is found on de surface of cewws, CD36 is dought to have a 'hairpin-wike' structure wif α-hewices at de C- and N- termini projecting drough de membrane and a warger extracewwuwar woop (Fig. 1). This topowogy is supported by transfection experiments in cuwtured cewws using dewetion mutants of CD36.[23][24]

Based on de crystaw structure of de homowogous SCARB2, a modew of de extracewwuwwar domain of CD36 has been produced.[25] Like SCARB2, CD36 is proposed to contain an antiparawwew β-barrew core wif many short α-hewices adorning it. The structure is predicted to contain a hydrophobic transport tunnew.
Disuwfide winkages between 4 of de 6 cysteine residues in de extracewwuwar woop are reqwired for efficient intracewwuwar processing and transport of CD36 to de pwasma membrane.[26] It is not cwear what rowe dese winkages pway on de function of de mature CD36 protein on de ceww surface.

Besides gwycosywation, additionaw posttranswationaw modifications have been reported for CD36. CD36 is modified wif 4 pawmitoyw chains, 2 on each of de two intracewwuwar domains.[24] The function of dese wipid modifications is currentwy unknown but dey wikewy promote de association of CD36 wif de membrane and possibwy wipid rafts which appear to be important for some CD36 functions.[27][28] CD36 couwd be awso phosphorywated at Y62, T92, T323,[29] ubiqwitinated at K56, K469, K472 and acetywated at K52, K56, K166, K231, K394, K398, K403.[30][31][32]

In de absence of wigand, membrane bound CD36 exists primariwy in a monomeric state. However exposure to de drombospondin wigand causes CD36 to dimerize. This dimerization has been proposed to pway an important rowe in CD36 signaw transduction.[33]

In humans, The gene is wocated on de wong arm of chromosome 7 at band 11.2 (7q11.2[34]) and is encoded by 15 exons dat extend over more dan 32 kiwobases. Bof de 5' and de 3' untranswated regions contain introns: de 5' wif two and de 3' one. Exons 1, 2 and first 89 nucweotides of exon 3 and as weww as exon 15 are non-coding. Exon 3 contains encodes de N-terminaw cytopwasmic and transmembrane domains. The C-terminaw cytopwasmic and transmembrane regions is encoded by exon 14. The extracewwuwar domain is encoded by de centraw 11 exons. Awternative spwicing of de untranswated regions gives rise to at weast two mRNA species.

On binding a wigand de protein and wigand are internawized. This internawization is independent of macropinocytosis and occurs by an actin dependent mechanism reqwiring de activation Src-famiwy kinases, JNK and Rho-famiwy GTPases.[35] Unwike macropinocytosis dis process is not affected by inhibitors of phosphatidywinositow 3-kinase or Na+/H+ exchange.

CD36 wigands have awso been shown to promote steriwe infwammation drough assembwy of a Toww-wike receptor 4 and 6 heterodimer.[36]

Recentwy, CD36 was winked to store-operated cawcium fwux, phosphowipase A2 activation, and production of prostagwandin E2[37]

Infections wif de human mawaria parasite Pwasmodium fawciparum are characterized by seqwestration of erydrocytes infected wif mature forms of de parasite and CD36 has been shown to be a major seqwestration receptor on microvascuwar endodewiaw cewws. Parasitised erydrocytes adhere to endodewium at de trophozoite/schizonts stage simuwtaneous wif de appearance of de var gene product (erydrocyte membrane protein 1) on de erydrocyte surface. The appearance of Pwasmodium fawciparum erydrocyte membrane protein 1 (PfEMP1) on de erydrocyte surface is a temperature dependent phenomenon which is due to increased protein trafficking to de erydrocyte surface at de raised temperature. PfEMP1 can bind oder endodewiaw receptors - drombospondin (TSP) and intercewwuwar adhesion mowecuwe 1 (ICAM-1) – in addition to CD36 - and genes oder dan PfEMP1 awso bind to CD36: cytoadherence winked protein (cwag) and seqwestrin. The PfEMP1 binding site on CD36 is known to be wocated on exon 5.

CD36 on de surface of de pwatewets has been shown to be invowved in adherence but direct adherence to de endodewium by de infected erydrocytes awso occurs. Autoaggregation of infected erydrocytes by pwatewets has been shown to correwate wif severe mawaria and cerebraw mawaria in particuwar and antipwatewet antibodies may offer some protection, uh-hah-hah-hah.

Severaw wines of evidence suggest dat mutations in CD36 are protective against mawaria: mutations in de promoters and widin introns and in exon 5 reduce de risk of severe mawaria. Gene diversity studies suggest dere has been positive sewection on dis gene presumabwy due to mawariaw sewection pressure. Dissenting reports are awso known
suggesting dat CD36 is not de sowe determinant of severe mawaria. In addition a rowe for CD36 has been found in de cwearance of gametocytes (stages I and II).

CD36 has been shown to have a rowe in de innate immune response to mawaria in mouse modews.[38] Compared wif wiwd type mice CD36 (-/-) mice de cytokine induction response and parasite cwearance were impaired. Earwier peak parasitemias, higher parasite densities and higher mortawity were noted. It is dought dat CD36 is invowved in de Pwasmodium fawciparumgwycophosphatidywinositow (PfGPI) induced MAPK activation and proinfwammatory cytokine secretion, uh-hah-hah-hah. When macrophages were exposed to PfGPI de proteins ERK1/2, JNK, p38, and c-Jun became phosphorywated. Aww dese proteins are invowved as secondary messengers in de immune response. These responses were bwunted in de CD36 (-/-) mice. Awso in de CD36 (-/-) macrophages secreted significantwy wess TNF-awpha on exposure to PfGPI. Work is ongoing to determine how dese exactwy how dese responses provide protection against mawaria.

CD36 is awso known as gwycoprotein IV (gpIV) or gwycoprotein IIIb (gpIIIb) in pwatewets and gives rise to de Nakaantigen. The Naka nuww phenotype is found in 0.3% of Caucasians and appears to be asymptomatic. The nuww phenotype is more common in African (2.5%), Japanese, and oder Asian popuwations (5-11%).

Mutations in de human CD36 gene were first identified in a patient who, despite muwtipwe pwatewettransfusions, continued to exhibit wow pwatewet wevews.[39][40] This condition is known as refractoriness to pwatewet transfusion, uh-hah-hah-hah. Subseqwent studies have shown dat CD36 found on de surface of pwatewets. This antigen is recognized by de monocwonaw antibodies (MAbs) OKM5 and OKM8. It is bound by de Pwasmodium fawciparum protein seqwestrin.[41]

Depending on de nature of de mutation in codon 90 CD36 may be absent eider on bof pwatewets and monocytes (type 1) or pwatewets awone (type 2). Type 2 has been divided into two subtypes - a and b. Deficiency restricted to de pwatewets awone is known as type 2a; if CD36 is awso absent from de erydobwasts de phenotype is cwassified as type 2b.[42] The mowecuwar basis is known for some cases: T1264G in bof Kenyans and Gambians; C478T (50%), 539 dewetion of AC and 1159 insertion of an A, 1438-1449 dewetion and a combined 839-841 dewetion GAG and insertion of AAAAC in Japanese.

In a study of 827 apparentwy heawdy Japanese vowunteers, type I and II deficiencies were found in 8 (1.0%) and 48 (5.8%) respectivewy.[43] In 1127 heawdy French bwood donors (awmost aww of whom were white Europeans) no CD36 deficiency was found.[44] In a second group onwy 1 of 301 white test subjects was found to be CD36 deficient. 16 of de 206 sub-Saharan bwack Africans and 1 of 148 bwack Caribbeans were found to be CD36 -ve. Three of 13 CD36 -ve persons examined had anti CD36 antibodies. In a group of 250 bwack American bwood donors 6 (2.4%) were found to be Naka antigen negative.[45]

CD36's association wif de abiwity to taste fats has made it a target for various studies regarding obesity and awteration of wipidtasting. CD36 mRNA expression was found to be reduced in taste bud cewws (TBC) of obese sand rats (P. obesus) compared to wean controws, impwicating an association between CD36 and obesity.[50] Awdough actuaw wevews of CD36 protein were not different between de obese and controw rat cewws, Abdouw-Azize et aw. hypodesize dat de physicaw distribution of CD36 couwd differ in obese rat cewws.[50] Changes in cawcium mediation have been associated wif CD36 and obesity as weww. Taste bud cewws (more specificawwy, cewws from de circumvawwate papiwwae) containing CD36 dat were isowated from obese mice exhibited a significantwy smawwer increase in cawcium after fatty acid stimuwation when compared to controw mice:[51] CD36 associated cawcium reguwation is impaired when mice are made to be obese (but not in normaw weight mice), and dis couwd be a mechanism contributing to behavior changes in de obese mice, such as decreased wipid taste sensitivity and decreased attraction to fats.[51]

There has been some investigation into human CD36 as weww. A study examined oraw detection of fat in obese subjects wif genetic bases for high, medium, and wow expression of de CD36 receptor. Those subjects wif high CD36 expression were eight times more sensitive to certain fats (oweic acid and triowein) dan de subjects wif wow CD36 expression, uh-hah-hah-hah.[17] Those subjects wif an intermediate amount of CD36 expression were sensitive to fat at a wevew between de high and wow groups.[17] This study demonstrates dat dere is a significant rewationship between oraw fat sensitivity and de amount of CD36 receptor expression, but furder investigation into CD36 couwd be usefuw for wearning more about wipid tasting in de context of obesity, as CD36 may be a target for derapies in de future.

Upreguwation of CD36 couwd contribute to membrane remodewing during senescence.[52] In response to various senescence‐inducing stimuwi, CD36 stimuwate NF-κB‐dependent infwammatory cytokine and chemokine production, a phenomenon known as de senescence‐associated secretory phenotype (SASP).[53] This secretory mowecuwe production weads to de onset of a comprehensive senescent ceww fate.

CD36 pways a rowe in de reguwation of angiogenesis, which may be a derapeutic strategy for controwwing de spread of cancer.[54] Some data from in vitro and animaw studies suggested dat fatty acid uptake drough CD36 may promote cancer ceww migration and prowiferation in hepatocewwuwar carcinoma, gwiobwastoma, and potentiawwy oder cancers; dere was wimited data from observationaw studies in peopwe dat wow CD36 may correwate wif a swightwy better outcome in gwiobwastoma.[55]